Virus-induced heart muscle disease occurs in approximately 5% of the human population. The susceptibility of individuals to this form of heart muscle disease must be under some form of genetic control both in respect to viral infection istself and the resulting inflammatory heart response. In this investigation we will examine the genetic role in coxsackie virus B3-induced murine heart muscle disease. Initially a panel of inbred mouse strains, varying at either the H-2 complex or non-H-2 loci, will be characterized for susceptibility to viral infection and to heart muscle inflammation and anti-viral/heart antibody production. These three parameters will be determined by virus replication assays, neutralization techniques, histological examination, ELISA procedures and immunofluorescence techniques. Genetic segregation analysis using H-2 congenic inbred lines will determine the number of loci involved in susceptibility and the inheritance patterns (dominance, recessiveness or co-dominance). Linkage studies using intra-H-2 recombinant strains for H-2 linked gene(s) and recombinant inbred lines for non-H-2 linked gene(s) will enable the mapping of these loci. The segregation and linkage analysis will be carried out through use of serologically detectable alloantigenic markers by hemagglutination and cytotoxlcity assays and of co-dominantly expressed biochemical markers by slab gel electrophoresis. We will also investigate the ability of the host to respond toward viral/heart antigens and the genetic control of these responses. These host responses will be analyzed by humoral techniques (ELISA, neutralization, immunofluorescence and absorption procedures) and by cellular assays (lymphocyte proliferation and cell-mediated-cytotoxicity assays). Characterization of the cells involved in the cellular immune responses will be done by negative selection and the antigens which these cells recognize defined by antibody blocking studies.